Intrinsic disorder: signaling via highly specific but short-lived association.
Intrinsic disorder: signaling via highly specific but short-lived association.
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DOI：
10.1016/j.tibs.2011.11.002
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发表时间：
2012-02
影响因子：
13.8
通讯作者：
Zhou, Huan-Xiang
中科院分区：
文献类型：
--
作者：
Zhou, Huan-Xiang
信号蛋白与其细胞靶点之间的结合通常被认为是高度特异性的（意味着高结合常数Ka），同时是瞬时的或短暂的（对应于高解离速率常数kd）。然而，高Ka和高kd的组合将导致高缔合速率常数（ka = Kakd），这带来了一个问题，因为存在ka可以增加的极限，该极限由扩散方法设定以形成络合物。在这个观点中，我建议在结合靶点之前使信号蛋白紊乱，这为摆脱这种困境提供了一种方法。信号传导蛋白的内在紊乱将降低Ka而不牺牲复合物的特异性，从而将允许kd增加到适合于信号传导的范围。
The association between signaling proteins and their cellular targets is generally thought to be highly specific (implicating a high association constant, Ka) and, at the same time, transient or short-lived (corresponding to a high dissociation rate constant, kd). However, a combination of high Ka and high kd would lead to a high association rate constant (ka = Kakd), which poses a problem because there is a limit to which ka can be increased, set by the diffusional approach to form the complex. In this Opinion, I propose that having the signaling protein disordered before binding the target provides a way out of this quandary. The intrinsic disorder of the signaling protein would decrease Ka without sacrificing the specificity of the complex, and thereby would allow kd to be increased to a range appropriate for signaling.
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